This project will examine the entrainment of circadian rhythms during early mammalian development. An critical feature of circadian regulation is the interaction of circadian oscillators with environmental cycles (entrainment) or with other circadian oscillators within the individuals organism. Such interactions establish specific, functionally important phase relationships among rhythms(temporal organization). A central hypothesis underlying research on human circadian rhythms is that the maintenance of temporal organization is important for human health. How circadian oscillators interact to maintain temporal organization is not understood. A unique opportunity to address this problem comes from a striking case of temporal organization that occurs during mammalian development; a circadian pacemaker in the offspring becomes entrained by the circadian pacemaker of the mother. Because the entrainment begins prenatally, this case of temporal organization provides a unique model in which the interactions between distinct and identified circadian pacemakers within the same physiological system(the mother) can be studied. The project will study the temporal relationship between the behavioral rhythms of the mother and her pups in the Syrian hamster(Mesocricetus auratur). Activity rhythms can be rigorously quantified only 35 days after fertilization and can be used to measure the relationships established by entrainment at an earlier age. Entrainment at early ages will also be directly tested by transplanting fetal tissue to an adult host and measuring the restored behavioral rhythms. Goals of the project are to identify the signals that mediate entrainment and to determine if there is a critical stage in pacemaker development when entrainment occurs. Of particular interest is the role of the pineal gland hormone, melatonin. Melatonin has already been implicated as an entraining signal and melatonin might have therapeutic applications for disorders related to circadian rhythms.